Varenicline Treatment for Cannabis Use Disorder

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT02892110
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 72
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.4
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

Marijuana is the most commonly used illicit drug. There is high demand for effective interventions for cannabis use disorder, yet few specific treatments for have been developed. This study will evaluate the efficacy of varenicline for reducing marijuana use in people who use marijuana frequently.

Condition or Disease	Intervention/Treatment	Phase
Substance Use Disorder	Drug: Varenicline; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Advancing Varenicline as a Treatment for Cannabis Use Disorder
• Actual Study Start Date: Feb 13, 2017
• Actual Primary Completion Date: Nov 8, 2018
• Actual Study Completion Date: Nov 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Varenicline 2 mg daily	Drug: Varenicline; 2 mg daily; Other Names: Chantix
Placebo Comparator: Placebo 2 mg daily	Drug: Placebo; 2 mg daily

Outcome Measures

Primary Outcome Measures

1. Cannabis Withdrawal Symptoms During Active Treatment [3 weeks (Week 4-6 of active treatment period)]

   For this outcome, the negative affect subscale items of The Cannabis Withdrawal Scale (items 5 ["I felt nervous], 6 ["I had some angry outbursts"], 7 ["I had mood swings"], 8 ["I felt depressed"], 9 ["I was easily irritated"], 15 ["Life seemed an uphill struggle"], 18 ["I felt physically tense"], restlessness (item 11, "I felt restless), and/or urge to smoke (items 1 and 10, "The only thing I could think about was smoking some cannabis" and "I had been imagining being stoned") were averaged at Weeks 4, 5, and 6 and for an overall 4-6 week value, with minimum score of the subscale being 0 and maximum score being 100 (higher score indicating worse outcome).

Secondary Outcome Measures

1. Number of Participants With Cannabis Abstinence [3 weeks (Week 4-6 of active treatment period)]

   Self reported abstinence from Timeline Followback, verified by urine cannabinoid measures

2. Cannabis Use Quantity [3 weeks (Week 4-6 of active treatment period)]

   Cannabis use sessions per day measured by Timeline Followback (self-report) at twice weekly visits during Weeks 4, 5 and 6 of the active treatment phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

General Inclusion Criteria

• Must meet DSM-5 criteria for cannabis use disorder and use cannabis at least 3 days per week in the last 30 days.

• Must be between the ages of 18 and 65 years.

• If female and of childbearing potential, must agree to use acceptable methods of birth control for the duration of the trial.

• Must consent to random assignment, and be willing to commit to medication ingestion.

• Must be able to read and provide informed consent.

• Must have body weight >110lbs (50kg) and have BMI between 18 and 35kg/m2

• Must function at an intellectual level and have knowledge of the English language to sufficiently allow for accurate completion of assessments.

Additional Inclusion Criteria for fMRI Eligibility

• Must be right-handed.

General Exclusion Criteria

• Women who are pregnant, nursing, or plan to become pregnant during the course of the study.

• Individuals with severe renal impairment (creatinine clearance less than 30 mL per minute).

• Lifetime history of DSM-5 Bipolar I or II Disorder, Schizophrenia or other psychotic disorder. Stably treated MDD, Dysthymia, GAD, Social Phobia, and Specific Phobia diagnoses are acceptable (i.e. same dose of medication has been prescribed for at least 2 months prior to screening and no changes in current medication expected during course of the trial).

• Suicidal ideation or behavior within the past 6 months. Subjects who are believed to be at suicidal or homicidal risk (answers 'yes' on questions 4 or 5 of C-SSRS) will be referred for assessment by a qualified mental health professional.

• Concomitant use of psychotropic medications, with the exception of stable doses (defined as no dosing adjustments in the past two months) of non-MAO-I antidepressants, non-benzodiazepine anxiolytics, and ADHD medications.

• Current use of medications prescribed for mania or psychosis.

• Current use of buproprion or nortryptiline.

• Moderate or severe non-cannabis substance use disorders within the past 60 days with the exception of tobacco use disorder.

• Individuals taking an investigational agent within the last 30 days before baseline visit.

• Individuals with clinically significant medical disorders or lab abnormalities.

• Any individual at screening with SGOT (AST) or SGPT (ALT) greater than 3 times the upper limit of normal and/or total bilirubin greater than two times the upper limit of normal.

• Individuals with clinically significant cardiovascular disease in the past 6 months (e.g., myocardial infarction, CABG, PTCA, severe or unstable angina, serious arrhythmia, or any clinically significant ECG conduction abnormality.

• Individuals with clinically significant cerebrovascular disease in the past 6 months such as TIA, CVA, or stroke.

• Hypersensitivity to varenicline.

• Individuals who have participated in the clinical trial of any investigative compound within the last 60 days.

Additional Exclusion Criteria for fMRI Eligibility

• Any psychiatric or medical issues, including claustrophobia, ferrous metal implants, pacemakers, or other electronic devices that would interfere with ability to participate in and successfully complete scanning procedures.

• Any person unable to lie still within the fMRI scanner for the required period of time to obtain useful images (use of anxiolytics will not be permitted for anxiety/claustrophobia related to scanning procedures).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Aimee McRae-Clark, PharmD, Medical University of South Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 12, 2018

More Information

Publications

None provided.

• Responsible Party: Aimee McRae-Clark, Professor of Psychiatry, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02892110
• Other Study ID Numbers: Pro00058198; UG3DA043231
• First Posted: Sep 8, 2016
• Last Update Posted: Dec 3, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aimee McRae-Clark, Professor of Psychiatry, Medical University of South Carolina: Marijuana use; Varenicline/Chantix; Motivational enhancement therapy
• Additional relevant MeSH terms: Substance-Related Disorders; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	2 mg daily Varenicline: 2 mg daily	2 mg daily Placebo: 2 mg daily
Period Title: Overall Study
STARTED	35	37
COMPLETED	22	25
NOT COMPLETED	13	12

Baseline Characteristics

Arm/Group Title	Varenicline	Placebo	Total
Arm/Group Description	2 mg daily Varenicline: 2 mg daily	2 mg daily Placebo: 2 mg daily	Total of all reporting groups
Overall Participants	35	37	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	37 100%	72 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	13 37.1%	10 27%	23 31.9%
Male	22 62.9%	27 73%	49 68.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.9%	3 8.1%	4 5.6%
Not Hispanic or Latino	34 97.1%	34 91.9%	68 94.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 45.7%	13 35.1%	29 40.3%
White	19 54.3%	23 62.2%	42 58.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 2.7%	1 1.4%
Region of Enrollment (participants) [Number]
United States	35 100%	37 100%	72 100%

Outcome Measures

1. Primary Outcome

Title	Cannabis Withdrawal Symptoms During Active Treatment
Description	For this outcome, the negative affect subscale items of The Cannabis Withdrawal Scale (items 5 ["I felt nervous], 6 ["I had some angry outbursts"], 7 ["I had mood swings"], 8 ["I felt depressed"], 9 ["I was easily irritated"], 15 ["Life seemed an uphill struggle"], 18 ["I felt physically tense"], restlessness (item 11, "I felt restless), and/or urge to smoke (items 1 and 10, "The only thing I could think about was smoking some cannabis" and "I had been imagining being stoned") were averaged at Weeks 4, 5, and 6 and for an overall 4-6 week value, with minimum score of the subscale being 0 and maximum score being 100 (higher score indicating worse outcome).
Time Frame	3 weeks (Week 4-6 of active treatment period)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	2 mg daily Varenicline: 2 mg daily	2 mg daily Placebo: 2 mg daily
Measure Participants	22	25
Overall Week 4-6 average	2.23 (4.65)	3.94 (6.23)
Week 4	2.59 (6.73)	4.07 (5.81)
Week 5	2.15 (4.84)	4.27 (7.11)
Week 6	1.96 (4.65)	3.47 (6.07)

2. Secondary Outcome

Title	Number of Participants With Cannabis Abstinence
Description	Self reported abstinence from Timeline Followback, verified by urine cannabinoid measures
Time Frame	3 weeks (Week 4-6 of active treatment period)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	2 mg daily Varenicline: 2 mg daily	2 mg daily Placebo: 2 mg daily
Measure Participants	22	25
Week 4	5 14.3%	3 8.1%
Week 5	4 11.4%	2 5.4%
Week 6	6 17.1%	2 5.4%

3. Secondary Outcome

Title	Cannabis Use Quantity
Description	Cannabis use sessions per day measured by Timeline Followback (self-report) at twice weekly visits during Weeks 4, 5 and 6 of the active treatment phase.
Time Frame	3 weeks (Week 4-6 of active treatment period)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	2 mg daily Varenicline: 2 mg daily	2 mg daily Placebo: 2 mg daily
Measure Participants	22	25
Week 4	0.93	1.33
Week 5	0.89	1.19
Week 6	0.89	1.21

Adverse Events

Time Frame	Adverse event data were collected from time of consent through last study visit (approximately 8 weeks).
Arm/Group Title	Varenicline		Placebo
Arm/Group Description	2 mg daily Varenicline: 2 mg daily		2 mg daily Placebo: 2 mg daily
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/37 (0%)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)		0/37 (0%)
Infections and infestations
Cellulitis	1/35 (2.9%)	1	0/37 (0%)	0
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/35 (85.7%)		32/37 (86.5%)
Gastrointestinal disorders
Fatigue	4/35 (11.4%)	4	1/37 (2.7%)	1
Nausea	16/35 (45.7%)	19	9/37 (24.3%)	10
Vomiting	6/35 (17.1%)	7	5/37 (13.5%)	7
Other GI	8/35 (22.9%)	9	9/37 (24.3%)	10
General disorders
Allergies	1/35 (2.9%)	1	4/37 (10.8%)	4
Dream disturbance	15/35 (42.9%)	15	7/37 (18.9%)	8
Headache	9/35 (25.7%)	11	12/37 (32.4%)	15
Insomnia	8/35 (22.9%)	8	9/37 (24.3%)	10
Irritability	2/35 (5.7%)	2	8/37 (21.6%)	9
Dizziness	3/35 (8.6%)	4	1/37 (2.7%)	1
Metabolism and nutrition disorders
Decreased appetite	4/35 (11.4%)	4	5/37 (13.5%)	5
Musculoskeletal and connective tissue disorders
Musculoskeletal	1/35 (2.9%)	1	4/37 (10.8%)	4
Respiratory, thoracic and mediastinal disorders
URI/cold symptoms	7/35 (20%)	8	7/37 (18.9%)	11

Limitations/Caveats

Intended as a proof of concept study; fully powered clinical trials are needed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.